Short term neoadjuvant androgen deprivation therapy does not affect prostate specific membrane antigen expression in prostate tissues

BACKGROUND. Prostate specific membrane antigen (PSMA) is a transmembrane gl ycoprotein highly expressed in benign prostate secretory-acinar epithelium and prostate carcinoma. The results of several studies suggest that PSMA ex pression is increased in prostate carcinoma cell lines subjected to androge n deprivation and in androgen-independent tumors. The authors studied the e ffects of short term (3-month) androgen deprivation on PSMA expression in p rostate carcinoma specimens using two anti-PSMA monoclonal antibodies (mAbs ), 7E11 and PM2J004.5. METHODS. The study included patients with clinically localized prostate car cinoma who were prospectively randomized into 1 of 2 treatment groups: 3 mo nths of neoadjuvant androgen deprivation therapy followed by radical prosta tectomy (ADT/RP), or radical prostatectomy (RP) alone. Representative forma lin fixed, paraffin embedded prostate sections were immunostained with the anti-PSMA mAbs 7E11 and PM2J004.5 by the streptavidin-biotin method. The au thors recorded the staining intensity and the percentage of positive cells stained in benign epithelium, high grade prostatic intraepithelial neoplasi a (PIN), and prostate carcinoma. They compared the results of 7E11 with tho se of PM2J004.5 in benign epithelium, high grade prostate, and carcinoma an d also compared the results between the two treatment groups (ADT/RP vs. RP alone). RESULTS. Both anti-PSMA mAbs stained benign secretory-acinar epithelium, hi gh grade PIN, and prostate carcinoma. In both treatment groups, PM2J004.5 r eacted with a significantly greater percentage of cells (P < 0.001) and wit h significantly greater intensity (P < 0.001) compared with 7E11 in benign epithelium and prostate carcinoma. With both anti-PSMA mAbs, the percentage of cells stained and the intensity of staining in high grade PIN was simil ar to that in prostate carcinoma. In the group that received RP alone, the percentage of cells stained and the intensity of staining with 7E11 were si gnificantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001), and the intensity of staining with the PM2J0 04.5 was significantly greater in high grade PIN and prostate carcinoma com pared with benign epithelium (P < 0.001). In the ADT/RP group, the percenta ge of cells stained and the intensity of staining with 7E11 and PM2J004.5 w ere significantly greater in prostate carcinoma compared with benign epithe lium (P < 0.006). PSMA staining did not correlate with either Gleason score (in the group that received RIP alone) or pathologic stage (in both the RP -alone and ADT/RP groups) and did not differ between the two treatment grou ps. CONCLUSIONS. Short term neoadjuvant ADT does not affect PSMA expression in benign prostate secretory-acinar epithelium, high grade PIN, or prostate ca rcinoma. Prostate carcinoma and high grade PIN express significantly higher levels of PSMA than benign prostate secretory-acinar epithelium. Compared with 7E11, the PM2J004.5 anti-PSMA mAb is a more sensitive immunohistochemi cal marker of prostate carcinoma in formalin fixed, paraffin embedded tissu e. (C) 2000 American Cancer Society.